In the description which follows, references are made to certain literature citations which are listed at the end of the specification.
Infections, trauma (e.g. falls, automobile accidents, gun and knife wounds), cardiovascular accidents (e.g. aneurysms and ischemic events often associated with surgery) and endogenous inflammatory reactions (e.g. pancreatitis and nephritis) often lead to profound dysfunction of the homeostatic mechanisms involved in regulating cardiovascular and immune system function.
Several conditions such as ischemia and infections, through inappropriate or excessive activation of the immune system, may result in cardiovascular dysfunction that develops over a period of hours to days. Compromised cardiovascular function increases morbidity and is life threatening.
Systemic inflammatory response syndrome (SIRS) is diagnosed largely on observed physiological changes such as increase (fever) or decrease in body temperature (hypothermia), increased heart rate (tachycardia), increased respiration rate (tachypnea), elevated or diminished white blood cell counts and inadequate perfusion of tissues and organs. Changes in blood pressure are not included in the definition because they occur late in the course of the syndrome. Decreases in blood pressure reflect the development of shock, and contribute to multiple organ failure, a leading cause of death in these patients. This definition of sepsis syndrome includes a large number of patients who exhibit similar physiological signals but have no evidence of any type of infection; other insults which induce a sepsis-like condition include pancreatitis, burns, ischemia, multiple trauma and tissue injury (often due to surgeries and transplants), haemorrhagic shock and immune-mediated organ dysfunction.
SIRS is the 13th leading cause of death in the United States of America. On average, 401 of sepsis syndrome patients are dead within 28 days of admission to intensive care.
The standard therapies for SIRS and septic shock involve administration of antibiotics to bring the infection under control and fluid/colloid therapy to maintain circulating blood volume. Frequently, drugs which help maintain blood pressure, such as dopamine and vasopressin, are also administered.
Recent strategies for developing more targeted therapies for the treatment of sepsis have been disappointing. In addition, many molecules in the new generation of anti-septic agents are very expensive and most possibly produce untoward immunological and cardiovascular reactions which make them contra-indicated in some cases of non-bacteremic shock.
Hypersensitivity to environmental antigens can, in severe cases, result in anaphylactic shock, which is treated by the administration of fluids and vasoactive agents to restore blood pressure.
There remains a need for inexpensive and effective agents for treatment of cardiovascular shock, sepsis, systemic inflammatory response syndrome and anaphylaxis.
The salivary glands are classically viewed as accessory digestive glands which mediate their actions through exocrine secretion, although appreciation has grown recently for the importance of their endocrine secretions (1-3). The exocrine secretion of biologically active peptides from the salivary glands is essential for the health of the mouth (4), whereas the endocrine secretions of these glands help maintain the structure and function of a large variety of internal tissues and organs such as the digestive tract (5-7), the mammary glands (8), the liver (9,10), and the reproductive tract (11,12). Rosinski-Chupin et al. (13,14) have described a protein from the male rat submandibular gland which is androgen-regulated and which they believed to have a male-specific function in the rate.
Another important action of salivary endocrine secretions is the modulation of the immune system, with effects being observed on lymphocyte (15,16), mast cell (17) and neutrophil (18,19) functions. The submandibular glands also regulate inflammatory reactions associated with the late-phase pulmonary inflammation induced by allergen in sensitized rats (20-22), and their removal exacerbates the severity of the hypotensive responses induced by intravenously administered lipopolysaccharide (LPS) (23). Removal of the submandibular glands, however, does not affect arterial blood pressure in the normal state (23).
In accordance with one embodiment, the invention provides a peptide of the formula: R1—X1—X2—R2                 wherein                    X1 is an aromatic amino acid residue;            X2 is any amino acid residue;            R1 is NH2— or an amino acid sequence X3—X4—X5                         wherein                    X3 is an aliphatic amino acid residue having a side chain hydroxyl group and            X4 and X5 are the same or different and are any amino acid residue and                        wherein                    R2 is a sequence of 1 to 3 amino acid residues which are the same or different and are aliphatic amino acid residues.                        
In accordance with a further embodiment, the invention provides a peptide having the amino acid sequence                Ser-Gly-Glu-Gly-Val-Arg (Sequence ID NO:1).        
In accordance with a further embodiment, the invention provides a method for treating or preventing SIRS-induced hypotension in a mammal comprising administering to the mammal an effective amount of a described peptide or of an effective fragment or derivative of the peptide.
In accordance with a further embodiment, the invention provides a method for treating or preventing anaphylactic hypotension in a mammal comprising administering to the mammal an effective amount of a described peptide or of an effective fragment or derivative of said peptide.
In accordance with a further embodiment, the invention provides a method of reducing or preventing an anaphylactic reaction in a mammal comprising administering an effective amount of a described peptide or of an effective fragment or derivative of said peptide to the mammal.
In accordance with a further embodiment, the invention provides a method of reducing or preventing an endotoxic reaction in a mammal comprising administering an effective amount of a described peptide or 11 or an effective fragment or derivative of said peptide to the mammal.
In accordance with a further embodiment, the invention provides a method for treating an inflammatory disorder in a mammal comprising administering to the mammal an effective amount of a described peptide or of an effective fragment or derivative of the peptide to the mammal.
In accordance with a further embodiment, the invention provides an antibody which specifically recognises an epitope of a peptide of the invention.
In accordance with a further embodiment, the invention provides a method of determining the peptide SGP-T or the peptide SGPS in a biological fluid comprising obtaining a sample of the biological fluid and determining the peptide in the fluid by immunoassay employing an antibody which specifically epitope of a peptide of the invention.